Current work is focused on the chronic-relapsing model experimental allergic encephalomyelitis (EAE). This disease is produced by transfer lymphocytes sensitized to myelin basic protein (MBP) or proteolipid protein to syngeneic mice. Neurologic dysfunction is characterized pathologically by inflammation and primary demyelination. The immunological mechanisms responsible for the initial episode and for the chronic disease are being investigated. Particular attention has focused on the role of activated T cells and regulatory mechanisms occurring at the level of EAE lesion. Recent studies have demonstrated that the administration of soluble MBP given the following cell transfer, or even after the onset of clinical disease, can ameliorate clinical illness. It is thought that the mechanism for this effect is the induction of apoptosis or programmed cell death. T cells which are activated and encounter antigen in the absence of a second signal i.e., IL-2, may be induced to undergo apoptosis. The effect of treatments which may alter cytokine profiles such as retinoic acid have been studied and found to reduce the severity of diseases. The biological mechanisms of retinoic acid treatment are being examined. To monitor the evolution of the EAE lesion, techniques have been developed to allow MRI studies of the mouse brain. Initial studies indicate that MRI changes correlate with inflammation and demyelination. This technique will be employed to monitor changes in the evolution of the lesion in parallel with immunological studies.